Radio-opaque isotropic fibre optic probes for in vivo photodynamic therapy dosimetry

Transcription

1 Radio-opaque isotropic fibre optic probes for in vivo photodynamic therapy dosimetry E.J. Hudson, M.R. Stringer, H.J. van Staveren*, M.. Smith cademic Unit of Medical Physics, Department of Clinical Medicine, University of Leeds, Welcome Wing, Leeds General Infirmary, Great George Street, Leeds LS 1 3EX, UK. *D Daniel den Hoed Cancer Centre, Groene Hilledijk, Rotterdam, The Netherlands. BSTRCT When measuring laser light distribution in tissue during photodynamic therapy, accurate determination of the position of the monitoring probes is vital. For this purpose, computerised tomographic scanning has been incorporated into our treatment routine. Different mixtures of barium sulphate powder and an opaque dental sealant were used in the construction of probes which could be imaged on a computerised tomographic scan. These were tested for radio-opacity, isotropy and strength, and a mixture of 27 % barium sulphate powder and 73 % opaque dental sealant was found to be suitable. 1. INTRODUCTION Isotropic fibre optic probes are used for both light delivery and for dosimetry studies in Photodynamic Therapy (PDT). For light detection purposes, three types of probes have been reported: those with a light scattering tip collect a fraction of the incident light1, while sapphire tipped probes2 and dye-doped probes3 both utilise fluorescence induced in the tip by the external light field. The former type of probe is the most sensitive whereas the latter two are reliably isotropic due to the inherent isotropic distribution of the induced fluorescence. In our application of PDT, skin carcinomas are treated by topical application of 5-aminolaevulinic acid followed by surface illumination using 630nm laser light. Prior to treatment, a number of small, scattering-type fibre optic probes are inserted under the skin surface and coupled to photodiode detectors in order to monitor the light dose received at depth. The position of the probe must be precisely defined in order to yield accurate dosimetry measurements1. O /94/$6.OO SPIE Vol. 2078/65

2 2. PROBE CONSTRUCTION Probes used for in vivo measurements are restricted in size by the bore of the hypodermic needle used to implant them (75Otm) and 2OOtm core optical fibre is used to allow adequate light collection. They must be strong enough to withstand implantation in tissue and demonstrate an isotropic response to the surrounding light field. 2.1 Cylindrical diffusing probes The initial patient dosimetry studies used short (2mm) cylindrical diffusing (CD) probes as light detectors4, inserted at a defined angle, with the depth beneath the surface calculated by geometrical means. These depth measurements were subsequently found to be inaccurate, possibly due to the non-rigid nature of tissue. For a more precise measurement of the probe depth beneath the skin, computerised tomographic scanning (CT) was introduced. Short lengths of copper wire were included in the tips of the probes in order to produce CT images (figure la). However, these probes were found to be less than ideal for the following reasons: The cylindrical nature of the probe does not yield a very isotropic response (figure 5). The position of the copper wire adjacent to the light detecting section may result in an error in the depth measurement. point of weakness exists where the fibre outer coating has been removed. Figure la. - : \ Silica Core \ \ Cladding \ 1-2mm Cylindrical Diffusing Sectj Outer Protective Coating Copper wire N Sealed End,..i. Figure lb. Diffusing Bulb 66 / SPIE Vol. 2078

3 2.2 Spherical diffusing probes It is possible to construct a different type of isotropic probe by coupling an optical fibre to the 488nm line from an rgon laser and so curing a near spherical bulb of dental paste on the output end. Commercially available dental sealants, e.g. Delton (Johnson & Johnson) contain a light-sensitive polymer and an opaque scatterer which gives the cured sealant a tooth-like appearance. The polymer is cured to a radius defined by the total energy delivered to it, and a near spherical tip is produced (figure ib). Dental sealants are also available without the scatterer, e.g. Heliobond (Vivadent) in which it is possible to add a scattering component. dding Barium Sulphate (Ba504) powder increases the scattering properties of the paste which reduces the scattering path length of the light within the paste and allows small diameter probes to give an increased isotropic response. 3.1 Radio-opacity 3. PROPERTIES OF SPHERICL PROBES CT numbers (Houndsfield Units) of spherical bulb probes embedded in a wax phantom were measured directly from the CT console by taking a cross-sectional cut through each probe (figure 2; table 1). The amount of Ba504 in each probe is indicated by the "effective mass" which is calculated by multiplying the % Ba504 by the volume of the probe, assuming the bulbs to be spherical. Figure 3 demonstrates the average effective mass of BaSO4 plotted against CT number, which shows a trend in increased CT number with increased barium. Figure 2 Figure 3 E 60,50. '4- o 40 U) 30 E U 4) C- C- II II hf CT Number SPIE Vol /67

4 Table 1 Mixture % Delton % Heliobond % BaSO CT No. (HU±5) RMS Deviation from 100% Isotropic Bi Effective mass (%BaSO4xV) B DB B B D FIBRE CD WX Strength Probe strength was measured by the force required to pull off a fibre tip. tensiometer was used to measure the maximum force for destruction. Chicken muscle was used, as a representation of human tissue, in the measurement of the force required to pull out the probes. In all cases, this was much lower than that needed for probe destruction (figure 4). Figure 4 10 Bulb Diameter (mm) U. I U S. # U U 1)1 C.) 0 L.1 j i Pull-off force. Pull-out force. 3.3 Isotropy The isotropy is indicated by a plot of percentage deviation from the mean fluence rate against angle, as measured in a goniometer. Table 1 details the root mean square (RMS) deviation from the 100% line, which indicates complete isotropy. Figure 5 shows traces from a "DB" probe and a "CD" probe. 68 I SPIE Vol. 2078

5 Figure 5 Figure ngle (degrees) 4. CONCLUSIONS Scattering bulb probes, made from the mixture of 73% Delton opaque dental paste and 27% Barium Sulphate powder (by weight) exhibit superior properties to the previously employed cylindrical diffusing probes. These probes are now used for in vivo dosimetry studies during PDT and can be seen imaged by CT scanning in figure CKNOWLEDGEMENTS Calum Youngson (Department of Restorative Dentistry, Leeds University) who generously provided the dental sealants. Staff at the Pharmacy Quality Control Laboratory, Bradford Royal Infirmary, for use of the tensiometer. Judith Clinkard and the staff of the CT scanning unit, Cookridge Hospital, Leeds. The Yorkshire Cancer Research Campaign. SPIE Vol / 69

6 6. REFERENCES 1. Hudson EJ, Stringer MR, Caimduff F, Smith M "In vivo light dosimetry during superficial photodynamic therapy" (These proceedings) 2. Bays R 1992 Ph.D. Thesis, Ecole Polytechnique Federale de Lausanne. "Instrumentation pour l'etude des proprietes optiques des tissus vivants." 3. Lilge L, Haw T, Wilson BC "Miniature isotropic optical fibre probes for quantitative light dosimetry in tissue" Phys. Med. Biol Feather JW, King PR, Driver I, Dawson JB 1989 " method for the construction of disposable cylindrical diffusing fibre optic tips for use in photodynamic therapy." Lasers Med. Sd Henderson B 1991 Ph.D. Thesis, Heriot Watt University, Edinburgh. "n isotropic dosimetry probe for monitoring light in tissue, theoretical and experimental assessment." 70 / SPIE Vol. 2078

7 Part Two PHOTODYNMIC THERPY OF CNCER